C H A P T E R

Swine Flu

12 Bala Vinoth, D Suresh Kumar

INTRODUCTION pulmonary diseases,

Influenza (the “flu”) is a seasonal respiratory illness caused
by influenza viruses. Influenza is usually a mild and self-
limited respiratory illness, but it has the potential to cause
significant morbidity & mortality as it spreads widely in
the community. In the last few years, we are experiencing
a new strain of Influenza A virus called Swine origin of
influenza virus (A/2009/H1N1). A highly contagious form
of human influenza virus related to a virus formerly
isolated from infected swine. The respiratory infection
popularly known as swine flu is caused by this influenza
virus first recognized in March 2009 and it speeded
quickly across other countries within short span of time
and resulted in recent big pandemic. This 2009 pandemic
influenza A (H1N1) virus is continued to co-circulate
following years along with seasonal influenza A and
cased significant mortality among young people.
EPIDEMIOLOGY
The latest pandemic of swine flu was first noted in
Mexico in March 2009, the outbreak rapidly spread
worldwide affected nearly 195 countries and finally
declared ended in August 2010. In India the  swine flu
outbreak killed 981 people in 2009 and 1763 in 2010.
The mortality decreased in 2011 to 75. However during
subsequent years the mortality gradually increased to 405
lives in 2012 and 699 lives in 2013. In 2015, the outbreak
became widespread throughout India. The states
of  Gujarat  and  Rajasthan  were the worst affected. H1N1
influenza A 2009 pandemic strain is now responsible for
periodic seasonal outbreaks of influenza in India.
The average incubation period is 1-3 days (maximum of
7 days) and the main mode of transmission is through
contact with large-particle respiratory droplets by
sneezing and coughing. Other body fluids (eg, diarrheal
stool) and fomites also play a role in transmission. Viral
shedding begins the day prior to symptom onset and
often to persist for five to seven days or even longer in
children and in immunocompromised individuals.
• Persons with hemodynamically significant cardiac
disease ( both congenital & acquired)
• Persons who have immunosuppressive disorders
or who are receiving immunosuppressive therapy
& HIV-infected persons
• Persons with sickle cell anemia and other
hemoglobinopathies
• Persons with diseases that requiring long-term
aspirin therapy,
• Persons with chronic renal dysfunction
• Persons with cancer
• Persons with chronic metabolic disease, such as
diabetes mellitus
• Persons with neuromuscular disorders, seizure
disorders, or cognitive dysfunction that may
compromise the handling of respiratory secretions
• Residents of any age of nursing homes or other
long-term care institutions
ETIOLOGICAL AGENT
The influenza virus is a RNA virus belonging to the family
Orthomyxoviridae with three main genera – Influenza A,
B and C. Influenza A is further sub-typed into 16 distinct
H types and 9 distinct N types based on the hemagglutinin
and neuraminidase antigens on the surface of the virus as
shown in the Figure 1.
Every year new strains of influenza virus emerge as its
Lipid bilayer
Hemagglutinin
(H)
RNA
and
Protein

RISK GROUPS Matrix protein

The risk factors for influenza complications are seen in
• Infants & children aged < 5 years and adults aged>
65 years
• Obese individuals
• Pregnant ladies Neuraminidase
(N)
• Persons with asthma or COPD & other chronic
Fig. 1: Structure of Influenza virus
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Table 1: Clinical features of Swine Influenza
Common clinical features Extra pulmonary manifestations Complications
Fever CVS: Chest pain, Hypotension Pulmonary: Progressive viral pneumonia,
secondary bacterial pneumonia, ARDS
Sore throat CNS: seizures, lethargy, altered Extra- Pulmonary:
mental status, weakness or paralysis CNS: Encephalitis, encephalopathy, GBS,
ADEM
Rhinorrhea Others: decreased urine output, CVS: Myocarditis, pericarditis
cyanosis, dehydration
Myalgia, arthralgia Others: renal failure, rhabdomyolysis, ryes
syndrome, hemophagocytosis, multi-organ

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failure syndrome
Headache
Vomiting, diarrhea

Table 2: Diagnostic tests for Swine Flu

Nonspecific findings:
CBC: Leucopenia, thrombocytopenia,
Anemia
LFT: Raised liver enzymes, & elevated
bilirubin
Others: Increased CPK & LDH
X-ray: Bilateral infiltrates (lower lobe
predominance) & features of ARDS
CT chest: Patchy consolidation or
ground glass opacities
Specific findings
RT- PCR: Highly sensitive * very high specific, usually recommended
test for clinical diagnosis faster turnaround time (nasopharyngeal or
throat swab in sick patient lower respiratory samples)
Viral culture: Moderately sensitive, highest specificity, usually
recommended for public health surveillance , not useful in clinical
situations due to long turnaround time
Rapid antigen test: The sensitivity widely varies and negative test will
not rule out influenza. Not recommended nowadays.

Table 3: Antiviral agents against Influenza

Oseltamivir (NA inhibitor)
Swine Influenza Susceptible
Seasonal H1N1 Mostly susceptible
Seasonal H3N2 Susceptible
Influenza B Susceptible
genes undergo point mutations leading to an ‘antigenic
drift’. This process helps the virus to evade host defense
mechanism. The influenza A virus is different when
compared to other two influenza viruses by having a
segmented genome with eight single stranded RNA
segments. When the host cell is infected with more than
one influenza virus, these genes have the opportunity
to get reassorted and produce a very different strain
altogether. This process is called ‘antigenic shift’ is mainly
responsible for pandemics strains of influenza viruses.
The current swine origin influenza A virus 2009 train has
undergone triple reassortment and contains genes from
the avian, swine and human viruses.
Zanamavir (Na inhibitor) Amantadine & Rimantadine
(M2 inhibitor)
Susceptible Resistant
Mostly susceptible Mostly resistant
Susceptible Resistant
Susceptible Resistant
other seasonal influenza virus, the A/2009/H1N1 virus
also binds to the 2, 3-linked sialic acid receptors that are
present in the lower respiratory tract and cause diffuse
alveolar damage. This finding may partially explain
the predilection of this new virus to cause pneumonia
in healthy individuals. After the initial illness, the
host usually mounts a protective mmune response
which involves a rise in antibody titers as well as T cell
activation. The production of interferon in the respiratory
mucosa is associated with a fall in virus shedding. Specific
histopathologic findings in the lungs included edema,
hyaline membranes , fibrin , hemorrhage , inflammation ,
type II pneumocyte hyperplasia and organizing fibrosis..

PATHOGENESIS  CLINICAL MANIFESTATIONS

Virus-containing droplet particles may settle on CASE DEFINITIONS
nasopharyngeal, tracheobronchial,conjunctival, or other Probable case of Influenza: (Influenza-like illness (ILI)) is
respiratory mucosal epithelial cells. In contrast to the defined as fever (temperature of 100ºF [37.8ºC] or greater)
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INFECTION
Fig. 2 Clinical algorithm for the management of suspected
Swine flu
with cough or sore throat in the absence of a known cause
other than influenza (Table 1).
A confirmed case of pandemic H1N1 influenza A is defined
as an individual with an ILI with laboratory-confirmed
H1N1 influenza A virus detection by real-time reverse
transcriptase polymerase chain reaction (rRT-PCR) or
culture (Table 2).
DIAGNOSIS
MANAGEMENT
Common anti-viral agents used to treat influenza viruses
are neuraminidase inhibitors and M protein inhibitors,
their activity against common influenza viruses are
shown in Table-3
INDICATIONS FOR TREATMENT
• Illness requiring hospitalization
• Progressive, severe, or complicated illness,
regardless of previous health status
• Extremes of age
• Pregnant women and women up to two weeks
postpartum
• Individuals with high risk medical conditions .and
those who were obese
PRIMARY REGIMENS FOR ADULTS
• Oseltamivir 75 mg po bid x 5 days OR Zanamivir 2
inhalations (5 mg each) bid x 5 days
• Oseltamavir can cause diarrhoea, nausea, vomiting
and abnormal behaviour. Zanamavir can cause
bronchospasm.
ALTERNATIVE & NEWER REGIMENS
Peramivir 600 mg (FDA approved for single dose
intravenous). It has got longer duration and may be
considered for severe disease). Commonest adverse effect
of peramivir is rash.
Zanamivir 600 mg  IV  q12h  for at least 5 days
(Investigational) can be considered for patients with
inability to take oseltamivir orally and contraindications
to inhaled zanamivir or who have progressive disease
despite at least 5 days of therapy, or suspected or
confirmed oseltamivir resistance.
OTHER SUPPORTIVE CARE
Supportive management including IV fluids, antipyretics,
and oxygen support for hypoxic patients and Low tidal
volume ventilation for mechanically ventilated patients
may be necessary. It is recommended that patients with
pandemic H1N1 influenza A, who developed pneumonia
be treated empirically for community-acquired
pneumonia (CAP) given the risk of secondary bacterial
pneumonia. Adjunctive approaches have been evaluated
including extracorporeal membrane oxygenation,
N-acetyl cysteine, and glucocorticoids, but further studies
are required to clearly know their role.
Clinical algorithm to manage swine flu is shown in Figure
2 below.
PREVENTION
Measures to prevent swine flu spread include use of face
mask (triple layer surgical mask), frequent hand wash
and adherence to cough etiquettes by the patient. Contact
surfaces should be disinfected with sodium hypochlorite
or household bleach 5%. Adult patients need to be
isolated till their symptoms had subsided. In children the
isolation period is little longer due to prolonged excretion
of viruses.
ANTIVIRAL PROPHYLAXIS 
The post exposure antiviral prophylaxis could be
considered for adults and children who had close contact
with a confirmed or suspected case and also fell into one
of the following categories:
• Adults who are at high risk for complications of
influenza
• Pregnant women and women who are up to two
weeks postpartum
• Children who are <5 years of age or who are at high
risk of complications of influenza
• Healthcare workers and emergency medical
personnel
DOSE & REGIMENS
Oseltamivir 75 mg po once daily for 10 days..
Zanamivir inhaled powder, 10 mg, once daily.
VACCINATION
The CDC\) recommended that H1N1 influenza vaccine be
given to all patients from six months of age and older.
Priority is given to health care personnel and the above
mentioned high risk groups.
Inactivated influenza vaccine (IIV), recombinant influenza
vaccine (RIV) and live attenuated influenza vaccine (LAIV)
are all what are available. IIV is the most common used.
The selection of vaccine subunits is based on the strain
prevalence during the previous year influenza activity.
Efficacy is 70 to 80 %. It takes 2 to 3 weeks for the immunity
to develop. Immunogenicity is retained if pandemic and
seasonal influenza vaccines are coadministered..
The small excess risk of Guillain-Barré syndrome and
narcolepsy is observed with the use of vaccine. Other
neurologic syndromes, such as transverse myelitis and
opsoclonus myoclonus syndrome has also been reported.
It is generally well tolerated and there is no safety concern
for the pregnant woman.
REFERENCES 53
1. Centers for Disease Control and Prevention (CDC). Update:
novel influenza A (H1N1) virus infections - worldwide,
May 6, 2009. MMWR Morb Mortal Wkly Rep 2009; 58:453.
2. World Health Organization. World now at the start of 2009
influenza pandemic.  http://www.who.int/mediacentre/
news/statements/2009/h1n1_pandemic_phase6_20090611/
en/index.html 
3. Clinical management of Human infection with pandemic
H1 N1 2009: Revised Guidance
4. Pandemic Influenza A H1N1 Clinical management protocol
& Infection control guidelines, Directorate General of
Health Services, Ministry of Health & Family Welfare,
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Government of India.
5. Harper SA et al. Expert Panel of the Infectious Diseases
Society of America. Seasonal influenza in adults and
children--diagnosis, treatment, chemoprophylaxis, and
institutional outbreak management: clinical practice
guidelines of the Infectious Diseases Society of America.
Clin Infect Dis 2009; 48:1003-32.